inhibit the TGF-β pathway, causes skin to revert back to a younger state

This sounds interesting. Hunt on for supplements that inhibit the TGF-β pathway?

https://medicalxpres...t-immunity.html

In mouse models, researchers used chemical blockers to inhibit the TGF-β pathway, causing the skin to revert back to a younger function and allowing dermal fibroblasts to convert into fat cells. Turning off the pathway in mice by genetic techniques had the same result.

Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta

https://www.cell.com...49?showall=true

Edited by stefan_001, 26 December 2018 - 07:57 PM.

Natural items that have been shown to decrease high TGF beta-1 are (about 1/2 way down entire page) ...

Is that what you wanted?

Natural items that have been shown to decrease high TGF beta-1 are (about 1/2 way down entire page) ...

 

Is that what you wanted?

Thanks, nice list.
 

I think this old friend is not included in the list:

https://www.ncbi.nlm...pubmed/23153811

 

 

Diabetes. 1997 Apr;46(4):671-81.

 

Nitric oxide inhibition of transforming growth factor-beta and collagen synthesis in mesangial cells.

 

Abstract

 

Culture of mesangial cells (MCs) in 5.6 vs. 30.0 mmol/l glucose for 3 weeks induced a sustained increase in protein kinase C (PKC) activity, transforming growth factor (TGF)-beta1 mRNA, bioactive TGF-beta, and collagen synthesis. Nitric oxide (NO), generated exogenously by the NO donor S-nitroso-N-acetyl, D,L-penicillamine (SNAP) or endogenously after the exposure of MC to interleukin-1beta (IL-1beta), suppressed bioactive TGF-beta in MCs cultured in 5.6 or 30.0 mmol/l glucose and suppressed or abolished increases in TGF-beta1 mRNA and collagen synthesis induced by high concentrations of glucose or phorbol 12,13-dibutyrate without altering values obtained with normal glucose concentrations. SNAP had a transient suppressive effect on PKC activity, which may explain at least in part some of the actions of SNAP. The selective inhibitor of PKC, bisindolylmaleimide (GFX), mimicked NO action. The ability of SNAP and IL-1beta to suppress TGF-beta and collagen synthesis was not mediated by cGMP, since the cGMP analog, 8-Br-PET-cGMP, did not mimic NO action and an antagonist of cGMP-dependent protein kinase, Rp-8-pCPT-cGMPs, did not prevent the inhibitory actions of SNAP. N-omega-L-arginine methyl ester (NMMA) increased TGF-beta in glomerular capillary endothelial cells (GCECs) and stimulated collagen synthesis by MC in a co-culture with GCECs. Captopril inhibited TGF-beta and collagen synthesis and increased cGMP in co-cultures of GCECs and MCs. These effects of captopril were abolished by NMMA, implying mediation by NO. Thus, endogenous NO produced by GCECs may modulate TGF-beta production by both GCECs and MCs and act to suppress matrix protein synthesis by MCs.

Nitric oxide, thats what you want 

 

Circ Res. 2005 Nov 25;97(11):1115-23. Epub 2005 Oct 20.

 

Nitric oxide regulates transforming growth factor-beta signaling in endothelial cells.

 

 

Abstract

 

Many forms of vascular disease are characterized by increased transforming growth factor (TGF)-beta1 expression and endothelial dysfunction. Smad proteins are a key step in TGF-beta-initiated signal transduction. We hypothesized that NO may regulate endothelial TGF-beta-dependent gene expression. We show that NO inhibits TGF-beta/Smad-regulated gene transactivation in a cGMP-dependent manner. NO effects were mimicked by a soluble analogue of cGMP. Inhibition of cGMP-dependent protein kinase 1 (PKG-1) or overexpression of dominant-negative PKG-1alpha suppressed NO/cGMP inhibition of TGF-beta-induced gene expression. Inversely, overexpression of PKG-1alpha catalytic subunit blocked TGF-beta-induced gene transactivation. Furthermore NO delayed and reduced phosphorylated Smad2/3 nuclear translocation, an effect mediated by PKG-1, whereas NG-nitro-L-arginine methyl ester augmented Smad phosphorylation and gene expression in response to TGF-beta. Aortas from endothelial NO synthase-deficient mice showed enhanced basal TGF-beta1 and collagen type I expression; endothelial cells from these animals showed increased Smad phosphorylation and transcriptional activity. Proteasome inhibitors prevented the inhibitory effect of NO on TGF-beta signaling. NO reduced the metabolic life of ectopically expressed Smad2 and enhanced its ubiquitination. Taken together, these results suggest that the endothelial NO/cGMP/PKG pathway interferes with TGF-beta/Smad2 signaling by directing the proteasomal degradation of activated Smad.

 

 

Nitric oxide regulates vascular calcification by interfering with TGF-β signalling 

 

Cardiovascular Research, Volume 77, Issue 1, 1 January 2008, Pages 221–230,https://doi.org/10.1093/cvr/cvm049

 

 

 

Abstract

 

Aims

Vascular calcification often occurs with advancing age, atherosclerosis, and metabolic disorders such as diabetes mellitus and end-stage renal disease. Vascular calcification is associated with cardiovascular events and increased mortality. Nitric oxide (NO) is crucial for maintaining vascular function, but little is known about how NO affects vascular calcification. The aim of this study was to examine the effect of NO on vascular calcification.

Methods and results

In this study, we examined the inhibitory effects of NO on calcification of murine vascular smooth muscle cells (VSMCs) in vitro. We measured calcium concentration, alizarin red staining, and alkaline phosphatase activity to examine the effect of NO on calcification of VSMCs and differentiation of VSMCs into osteoblastic cells. We also determined gene expression and levels of phosphorylation of Smad2/3 by RT–PCR and western blotting. NO inhibited calcification of VSMCs and differentiation of VSMCs into osteoblastic cells. An inhibitor of cyclic guanosine monophosphate (cGMP)-dependent protein kinase restored the inhibition by NO of osteoblastic differentiation and calcification of VSMCs. NO inhibited transforming growth factor-β (TGF-β)-induced phosphorylation of Smad2/3 and expression of TGF-β-induced genes such as plasminogen activator inhibitor-1. In addition, NO inhibited expression of the TGF-β receptor ALK5.

Conclusion

Our data show that NO prevents differentiation of VSMCs into osteoblastic cells by inhibiting TGF-β signalling through a cGMP-dependent pathway. Our findings suggest that NO may play a beneficial role in atherogenesis in part by limiting vascular calcification.

Edited by Phoebus, 28 December 2018 - 02:54 AM.

@Phoebus Nice find! But how to raise that...L-Argine?

Edited by stefan_001, 28 December 2018 - 09:44 PM.

@Phoebus Nice find! But how to raise that...L-Argine?

well, what about topical NO? 

this study shows that it can be done, if you dont use an acidic base for the NO cream 

https://www.scienced...022202X15337465

also - "The mechanism by which minoxidil promotes hair growth is not fully understood. Minoxidil contains the nitric oxide chemical moiety, and may act as a nitric oxide agonist."

so topically applied NO is possible and has been shown to be mostly safe. 

But I have no idea how one would go about making an NO cream 

Edited by Phoebus, 29 December 2018 - 06:38 PM.

On the same ScienceDirect page I came across a full discussion of topically applying NO. Difficult but not impossible, the authors say. The latest promising experiment is to combine NO with a zeolite cream.

https://www.scienced...022202X15337477

Interestingly zeolite creams are readily available. So how to mix in your NO?

SB414 nitric oxide-releasing cream has recently passed phase Ib trial and data has been released mid december. Phase II trial to be launched in the next future:

https://www.apnews.com/24e4126e57544b04410dbcafd54b2fb5

SB414 nitric oxide-releasing cream has recently passed phase Ib trial and data has been released mid december. Phase II trial to be launched in the next future:

 

https://www.apnews.com/24e4126e57544b04410dbcafd54b2fb5

oh very interesting. Looks to be prescription though i would imagine. Wonder how hard it would be to get hold of? 

Great finds / Ideas.

Seems you can buy acne creams that contain NO:

https://www.amazon.c...xide+cream&th=1

"The power of Nitric Oxide"  No nitric oxide though if I read correctly.

Great finds / Ideas.

 

Seems you can buy acne creams that contain NO:

 

https://www.amazon.c...xide+cream&th=1

"sodium nitrite"

seems like thats the ingredient they are claiming will create NO, but will it? 

@Phoebus Nice find! But how to raise that...L-Argine?

High doubts raised on acute L-arginine dose rising NO levels in healthy individuals:

https://www.ncbi.nlm...les/PMC3489573/

Being NO a gas, mixing it in DMSO, for sample, will give us a fizzy stuff funny tickling on our skin. Perhaps an NO emulsion:

https://www.ncbi.nlm...les/PMC4136763/

now I'm actually really interested in whether sodium nitrite, applies topically, would create NO. 

I have come across several studies which show IV sodium nitrite does in fact create NO in the body, but it does so via 'an enzymatic process'

would that same process happen if you apply it topically? 

no clue 

Edited by Phoebus, 31 December 2018 - 10:15 PM.

In the treatment group, in addition to routine care (change positions, rinsing, and dressing) nitric oxide releasing cream [sodium nitrite 6% + citric acid (monohydrate) 9%] was used in the ulcer site. Each substance was prepared with a separate cream base. First, citric acid was applied on the ulcer surface and spread evenly over the ulcer. Then, equal amount of sodium nitrite was rubbed on the ulcer and gently mixed with citric acid.[32,40] By acidification of nitrite (NO2), nitric oxide is released from dinitrogen trioxide interface (N2O3).[32,33,40,53]

https://www.ncbi.nlm...les/PMC4857669/